The goals of the proposed work are (1) to establish a role of cortico-cortical feedback in visual decision- making, (2) to examine a potential link between top-down cortico-cortical feedback such as feature-based attention and decision-related activity in visual neurons and (3) to expand the candidate's experimental expertise by optogenetic techniques in behaving primates. Achieving the third objective will complement the candidate's previous training in awake behaving primate visual neurophysiology. Achieving the first and second objective will provide a launching point for the candidate to develop an independent research career, toward a long-term goal of an improved understanding of the role of feedback in perceptual decision-making. These objectives will be accomplished in two phases. In the 2-year mentored phase, the candidate will conduct supervised research in Dr. Callaway's and Dr. Reynolds' laboratory at the Salk Institute to develop and use optogenetic techniques to characterize cortico-cortical feedback connections to V1 (Aim 1) in fixating monkeys. This training environment is uniquely suitable because of Dr. Callaway's expertise in developing genetic techniques for neurobiology combined with Dr. Reynolds' expertise in the study of attention in primates, the immediate availability of monkeys and the intellectual resources available at the Salk Institute, in molecular neurobiology, genetic techniques, viral vectors, neuro-anatomy, visual neuroscience and theoretical neuroscience. In the next 3-year phase, the candidate's independent research will test the hypothesis that decision-related activity in V1, and modulation by feature-based attention in these areas, share a common mechanism, using single unit neurophysiological recordings (Aim 2), and optogenetic techniques (Aim 3). Aim 3 will at the same time allow the candidate to examine the role of cortico-cortical feedback from V2 to V1 in visual decision-making. It represents an innovative approach to study the role of cortical circuits, a merging of established lines of research (attention and perceptual decision-making) and will advance our understanding of the neural circuitry involved in the dynamic processes of cortico-cortical feedback underlying decision making. Impaired control of cortico-cortical feedback appears to be involved in brain disorders such as schizophrenia. Understanding the role of cortico-cortical feedback may therefore inform clinical treatments for patients with schizophrenia. PUBLIC HEALTH RELEVANCE: Relevance to public health The read-out of visual cortex serves as a model system for interpretation, decision-making and reasoning. This area therefore sheds light on brain functions central to brain disorders affecting higher mental function, such as Alzheimer's disease, Schizophrenia and neglect. Ultimately, a better understanding of the role of cortico-cortical feedback and of how activity in cortical areas is related to perception, decisions and behavior may also allow the development of more sophisticated neural prostheses.